1. Field of the Invention
The present invention provides pharmaceutical compositions comprising at least one dimethane sulfonate compound and methods for treating patients suffering from or susceptible to renal cancer by administration of a dimethane sulfonate compound to the patient.
2. Background
Renal cell carcinoma (RCC) in humans is one of the most difficult malignancies to treat. Few effective therapies have been found; presently, only biological therapy offers some minimal benefit for patients with this disease. The mechanism of the extensive drug resistance observed in RCC has not been elucidated, although expression of membrane transporters and metabolism have been suggested. Few antineoplastic compounds have been developed in a specific search for agents active against this disease.
RCC accounts for 3% of all adult male malignancies in the United States and is a clinicopathologically heterogeneous disease that includes several histologically distinct cellular subtypes. A majority of the published evidence suggests that proximal renal tubules are the sites from which malignant RCC cells originate, although a recent study offers evidence that such cells may also originate from distal tubules. RCC also frequently develops in conjunction with polycystic kidney disease and renal allografts, both of which conditions induce a chronic regenerative response.
Certain dimethane sulfonate compounds (e.g., NSC-268965, 280074, 281613, and 281817) were identified as having in vitro activity against RCC tumor cell lines. However, antitumor activity of these compounds in xenograft-bearing mice was only modest. See, Mertins et al. (Clinical Cancer Research, (2001) 7:620-633) and Mertins et al. (Molecular Cancer Therapy, (2004) 3(7) 549-860). Each of the compounds possess in vivo antitumor activity at high dosages and only a few animals were tumor free.
NSC-281612 is a dimethane sulfonate compound which was first prepared in the 1960's as a synthetic intermediate in the preparation of various Schiff base compounds. See, Elderfield, et al., Journal of Organic Chemistry. (1962) 27, 573-575, Chaudhari, et al., Bull. Haff. Instt. (1975) 3:1, 20-26, and Chaudhari, et al., Bull. Haffi Instt. (1975) 3:2, pp 81-90. Elderfield also reports, based on a private communication, that NSC-281612 possesses activity against Dunning rat leukemia (see Elderfield, page 574, left column lines 11-5 from the bottom of the page). No specific data was disclosed.
At present, treatment of renal cell carcinoma has been limited by an absence of selective and high activity anti-tumor agents and methods of treating tumors in a patient. Thus, it would be desirable to provide new therapeutic protocols for treatment of renal cancer. In particular, it would be desirable to provide new administration protocols for dimethane sulfonate compounds which reduce or eliminate renal cancer cells or tumors.